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Article

Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus

by
Adiel Ortega-Ayala
1,2,3,4,†,
Carla González de la Cruz
2,3,4,†,
Lorena Mora
5,6,
Mauro Bonilla
6,
Leandro Tana
6,
Fernanda Rodrigues-Soares
2,3,4,7,
Pedro Dorado
2,4,
Adrián LLerena
2,3,4,* and
Enrique Terán
4,6,*
1
Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
2
Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain
3
Pharmacogenomics and Personalized Medicine Unit, Badajoz University Hospital, Extremadura Health Service SES, 06006 Badajoz, Spain
4
RIBEF Red Iberoamericana de Farmacogenégica y Farmacogenómica SIFF, 06080 Badajoz, Spain
5
Laboratorio Clínico, Dispensario Central del Instituto Ecuatoriano de Seguridad Social (IESS), Quito 170901, Ecuador
6
Colegio de Ciencias de la Salud, Universidad San Francisco de Quito (USFQ), Quito 170901, Ecuador
7
Department of Pathology, Genetic and Evolution, Universidade Federal do Triângulo Mineiro, Uberaba 38025-350, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceuticals 2025, 18(9), 1335; https://doi.org/10.3390/ph18091335
Submission received: 6 August 2025 / Revised: 1 September 2025 / Accepted: 3 September 2025 / Published: 5 September 2025

Abstract

Background/Objectives: In Ecuador, the prevalence of type 2 diabetes mellitus (T2DM) is the second leading cause of death after ischemic heart disease. Genetic variability in protein-coding genes, single nucleotide variants (SNVs), influences the response to antidiabetic drugs. The frequency of SNVs varies among different populations, so studying the ancestral proportions among SNVs is important for personalized medicine in the treatment of T2DM. This study aimed to evaluate the distribution of Native American, European, and African (NATAM, EUR, and AFR) ancestry in 23 allelic variants of the seven genes that encode the relevant enzymes that metabolize antidiabetic drugs in an Ecuadorian population. Methods: Twenty-three allelic variants of seven genes were analyzed in 297 patients with T2DM from Ecuador, and the molecular ancestry of the samples was analyzed considering three ancestral groups, NATAM, EUR, and AFR using 90 ancestry informative markers (AIMs). Allele and ancestry distributions were analyzed using Spearman’s correlation. Results: The Ecuadorian population presents NATAM (61.33%), EUR (34.48%), and AFR (2.60%) ancestry components. CYP2C8*1 and CYP2C9*1 were positively related to NATAM ancestry, while CYP2C8*4 and CYP2C9*2 were positively related to EUR ancestry. CYP2C19*17 was positively correlated to AFR ancestry. The correlation of SLC22A1 variants such as A in rs594709 was positively correlated with NATAM, while GAT in rs72552763 was positive for EUR. The G variant of rs628031 of the SLC22A1 gene was positively correlated with NATAM and negatively correlated with EUR. The C variant of rs2076828 of the SLC22A3 gene was positively correlated with NATAM ancestry. Conclusions: In the Ecuadorian population, a predominance of Native American ancestry has been observed. Among the allelic variants related to enzymes that metabolize antidiabetic drugs, a relationship has been observed between this ancestral component and variants of the CYP2C8*1, CYP2C9*1, SLC22A1 (rs594709 and rs628031), and SLC22A3 (rs2076828) genes. This information is fundamental for the development of strategies for the implementation of personalized medicine programs for Latin American patients.
Keywords: antidiabetic drugs; T2DM; CYP2C8; CYP2C9; CYP2C19; molecular ancestry; SLC22 family antidiabetic drugs; T2DM; CYP2C8; CYP2C9; CYP2C19; molecular ancestry; SLC22 family
Graphical Abstract

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MDPI and ACS Style

Ortega-Ayala, A.; de la Cruz, C.G.; Mora, L.; Bonilla, M.; Tana, L.; Rodrigues-Soares, F.; Dorado, P.; LLerena, A.; Terán, E. Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus. Pharmaceuticals 2025, 18, 1335. https://doi.org/10.3390/ph18091335

AMA Style

Ortega-Ayala A, de la Cruz CG, Mora L, Bonilla M, Tana L, Rodrigues-Soares F, Dorado P, LLerena A, Terán E. Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus. Pharmaceuticals. 2025; 18(9):1335. https://doi.org/10.3390/ph18091335

Chicago/Turabian Style

Ortega-Ayala, Adiel, Carla González de la Cruz, Lorena Mora, Mauro Bonilla, Leandro Tana, Fernanda Rodrigues-Soares, Pedro Dorado, Adrián LLerena, and Enrique Terán. 2025. "Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus" Pharmaceuticals 18, no. 9: 1335. https://doi.org/10.3390/ph18091335

APA Style

Ortega-Ayala, A., de la Cruz, C. G., Mora, L., Bonilla, M., Tana, L., Rodrigues-Soares, F., Dorado, P., LLerena, A., & Terán, E. (2025). Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus. Pharmaceuticals, 18(9), 1335. https://doi.org/10.3390/ph18091335

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